PACAP and its receptors in migraine pathophysiology

Pituitary adenylate cyclase-activating peptide (PACAP) and its receptors (PAC1 , VPAC1 and VPAC2 ) are present in sensory neurons and in vascular smooth muscle related to the trigeminovascular system, a key factor in migraine pain. Recent data point to an involvement of PACAP, and in particular the PAC1 receptor, in the pathophysiology of migraine. Available data are discussed in relation to a study by Walker in this issue of the Journal with the goal of identifying possibilities for the development of novel antagonists and to further define the role of PACAP in migraine pathophysiology and as a new target for antimigraine therapeutics.